The role of mitochondria in the gut-kidney axis: implications for kidney health

Mitochondria, multifunctional organelles that regulate cellular energy metabolism and signaling pathways, play a pivotal role in maintaining the physiological functions of the gut and kidneys, as well as influencing the progression of chronic kidney disease (CKD). Through the gut-kidney crosstalk, gut microbiota modulate gut and renal pathophysiology and also influence mitochondrial activity in intestinal and renal cells. This review explores the regulatory roles of mitochondria in preserving epithelial barrier integrity, regulating intestinal metabolism, and maintaining gut microbiota homeostasis. It also examines the contributions of mitochondrial biogenesis, dynamics, autophagy abnormalities, and mitochondrial DNA (mtDNA) damage to renal pathological progression. Moreover, we highlight the bidirectional interactions between intestinal and renal mitochondria via the microbiota-mitochondria-kidney axis and mechanisms involving inflammation, oxidative stress, and ferroptosis. Therefore, targeting mitochondrial regulation through non-pharmacological interventions such as dietary adjustments, probiotic supplementation and fecal microbiota transplantation (FMT) emerges as a promising therapeutic strategy for maintaining renal health by optimizing mitochondrial function. In conclusion, elucidating the mechanisms of mitochondrial involvement in the gut-kidney axis will lay the foundation for novel therapeutic approaches to CKD and other gut-kidney axis-related disorders.